Dawkins begins by discussing the altruism that people display, indicating that he will argue it is explained by gene selfishness, and attacking group selection as an explanation. He considers the origin of life with the arrival of molecules able to replicate themselves. From there, he looks at DNA's role in evolution, and its organisation into chromosomes and genes, which in his view behave selfishly. He describes organisms as apparently purposive but fundamentally simple survival machines, which use negative feedback to achieve control. This extends, he argues, to the brain's ability to simulate the world with subjective consciousness, and signalling between species. He then introduces the idea of the evolutionarily stable strategy, and uses it to explain why alternative competitive strategies like bullying and retaliating exist. This allows him to consider what selfishness in a gene might actually mean, describing W. D. Hamilton's argument for kin selection, that genes for behaviour that improves the survival chances of close relatives can spread in a population, because those relatives carry the same genes.

Dawkins examines childbearing and raising children as evolutionary strategies. He attacks the idea of group selection for the good of the species as proposed by V. C. Wynne-Edwards, arguing instead that each parent necessarily behaves selfishly. A question is whether parents should invest in their offspring equally or should favour some of them, and explains that what is best for the survival of the parents' genes is not always best for individual children. Similarly, Dawkins argues, there are conflicts of interest between males and females, but he notes that R. A. Fisher showed that the optimal sex ratio is 50:50. He explains that this is true even in an extreme case like the harem-keeping elephant seal, where 4% of the males get 88% of copulations. In that case, the strategy of having a female offspring is safe, as she'll have a pup, but the strategy of having a male can bring a large return (dozens of pups), even though many males live out their lives as bachelors. Amotz Zahavi's theory of honest signalling explains stotting as a selfish act, he argues, improving the springbok's chances of escaping from a predator by indicating how difficult the chase would be.

Dawkins discusses why many species live in groups, achieving mutual benefits through mechanisms such as Hamilton's selfish herd model: each individual behaves selfishly but the result is herd behaviour. Altruism too can evolve, as in the social insects such as ants and bees, where workers give up the right to reproduce in favour of a sister, the queen; in their case, the unusual (haplodiploid) system of sex determination may have helped to bring this about, as females in a nest are exceptionally closely related.

The final chapter of the first edition introduced the idea of the meme, a culturally-transmitted entity such as a hummable tune, by analogy to genetic transmission. Dawkins describes God as an old idea which probably arose many times, and which has sufficient psychological appeal to survive effectively in the meme pool. The second edition (1989) added two more chapters.